Prebiotic inulin enhances gut microbial metabolism and anti-inflammation in apolipoprotein E4 mice with sex-specific implications
Abstract Gut dysbiosis has been identified as a crucial factor of Alzheimer's disease (AD) development for apolipoprotein E4 (APOE4) carriers. Inulin has shown the potential to mitigate dysbiosis. However, it remains unclear whether the dietary response varies depending on sex. In the study, we...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-09-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-42381-x |
| _version_ | 1797453112905039872 |
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| author | Ya-Hsuan Chang Lucille M. Yanckello George E. Chlipala Stefan J. Green Chetan Aware Amelia Runge Xin Xing Anna Chen Kathryn Wenger Abeoseh Flemister Caixia Wan Ai-Ling Lin |
| author_facet | Ya-Hsuan Chang Lucille M. Yanckello George E. Chlipala Stefan J. Green Chetan Aware Amelia Runge Xin Xing Anna Chen Kathryn Wenger Abeoseh Flemister Caixia Wan Ai-Ling Lin |
| author_sort | Ya-Hsuan Chang |
| collection | DOAJ |
| description | Abstract Gut dysbiosis has been identified as a crucial factor of Alzheimer's disease (AD) development for apolipoprotein E4 (APOE4) carriers. Inulin has shown the potential to mitigate dysbiosis. However, it remains unclear whether the dietary response varies depending on sex. In the study, we fed 4-month-old APOE4 mice with inulin for 16 weeks and performed shotgun metagenomic sequencing to determine changes in microbiome diversity, taxonomy, and functional gene pathways. We also formed the same experiments with APOE3 mice to identify whether there are APOE-genotype dependent responses to inulin. We found that APOE4 female mice fed with inulin had restored alpha diversity, significantly reduced Escherichia coli and inflammation-associated pathway responses. However, compared with APOE4 male mice, they had less metabolic responses, including the levels of short-chain fatty acids-producing bacteria and the associated kinases, especially those related to acetate and Erysipelotrichaceae. These diet- and sex- effects were less pronounced in the APOE3 mice, indicating that different APOE variants also play a significant role. The findings provide insights into the higher susceptibility of APOE4 females to AD, potentially due to inefficient energy production, and imply the importance of considering precision nutrition for mitigating dysbiosis and AD risk in the future. |
| first_indexed | 2024-03-09T15:18:13Z |
| format | Article |
| id | doaj.art-17627065e65e4ee9836fbd65ec622a26 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-09T15:18:13Z |
| publishDate | 2023-09-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-17627065e65e4ee9836fbd65ec622a262023-11-26T12:58:19ZengNature PortfolioScientific Reports2045-23222023-09-0113111510.1038/s41598-023-42381-xPrebiotic inulin enhances gut microbial metabolism and anti-inflammation in apolipoprotein E4 mice with sex-specific implicationsYa-Hsuan Chang0Lucille M. Yanckello1George E. Chlipala2Stefan J. Green3Chetan Aware4Amelia Runge5Xin Xing6Anna Chen7Kathryn Wenger8Abeoseh Flemister9Caixia Wan10Ai-Ling Lin11Department of Pharmacology and Nutritional Sciences, University of KentuckyDepartment of Pharmacology and Nutritional Sciences, University of KentuckyResearch Informatics Core, University of Illinois ChicagoGenomics and Microbiome Core Facility, Rush UniversityDepartment of Radiology, University of MissouriDepartment of Biological Sciences, University of MissouriDepartment of Radiology, University of MissouriSanders Brown Center on Aging, University of KentuckyDepartment of Biochemistry, University of MissouriDepartment of Radiology, University of MissouriDepartment of Biological and Biomedical Engineering, University of MissouriDepartment of Pharmacology and Nutritional Sciences, University of KentuckyAbstract Gut dysbiosis has been identified as a crucial factor of Alzheimer's disease (AD) development for apolipoprotein E4 (APOE4) carriers. Inulin has shown the potential to mitigate dysbiosis. However, it remains unclear whether the dietary response varies depending on sex. In the study, we fed 4-month-old APOE4 mice with inulin for 16 weeks and performed shotgun metagenomic sequencing to determine changes in microbiome diversity, taxonomy, and functional gene pathways. We also formed the same experiments with APOE3 mice to identify whether there are APOE-genotype dependent responses to inulin. We found that APOE4 female mice fed with inulin had restored alpha diversity, significantly reduced Escherichia coli and inflammation-associated pathway responses. However, compared with APOE4 male mice, they had less metabolic responses, including the levels of short-chain fatty acids-producing bacteria and the associated kinases, especially those related to acetate and Erysipelotrichaceae. These diet- and sex- effects were less pronounced in the APOE3 mice, indicating that different APOE variants also play a significant role. The findings provide insights into the higher susceptibility of APOE4 females to AD, potentially due to inefficient energy production, and imply the importance of considering precision nutrition for mitigating dysbiosis and AD risk in the future.https://doi.org/10.1038/s41598-023-42381-x |
| spellingShingle | Ya-Hsuan Chang Lucille M. Yanckello George E. Chlipala Stefan J. Green Chetan Aware Amelia Runge Xin Xing Anna Chen Kathryn Wenger Abeoseh Flemister Caixia Wan Ai-Ling Lin Prebiotic inulin enhances gut microbial metabolism and anti-inflammation in apolipoprotein E4 mice with sex-specific implications Scientific Reports |
| title | Prebiotic inulin enhances gut microbial metabolism and anti-inflammation in apolipoprotein E4 mice with sex-specific implications |
| title_full | Prebiotic inulin enhances gut microbial metabolism and anti-inflammation in apolipoprotein E4 mice with sex-specific implications |
| title_fullStr | Prebiotic inulin enhances gut microbial metabolism and anti-inflammation in apolipoprotein E4 mice with sex-specific implications |
| title_full_unstemmed | Prebiotic inulin enhances gut microbial metabolism and anti-inflammation in apolipoprotein E4 mice with sex-specific implications |
| title_short | Prebiotic inulin enhances gut microbial metabolism and anti-inflammation in apolipoprotein E4 mice with sex-specific implications |
| title_sort | prebiotic inulin enhances gut microbial metabolism and anti inflammation in apolipoprotein e4 mice with sex specific implications |
| url | https://doi.org/10.1038/s41598-023-42381-x |
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